Progress 10/01/06 to 12/31/08
Outputs
OUTPUTS: Pyrroloquinoline quinone (PQQ) and/or its principle derivatives, imidazolopyrroloquinoline quinone (IPQ), are present in tissues and biological fluids at concentrations ranging from nanomolar to micromolar concentrations. PQQ elicits and modulates both physiological and developmental characteristics in experimental animal models (rats and mice), particularly during periods of neonatal growth. However, the exact biological function(s) of PQQ remain(s) unclear. Using gene array and cell biology approaches, we completed work with the objectives of demonstrating mechanistically how PQQ improves physiological and developmental characteristics important to growth and development. Several animal model approaches were also developed to study cell signaling and expression of low-level genes. The work was presented at the Second International Interdisciplinary Conference on Vitamins, Coenzymes, and Biofactors in Athens, GA and sessions at Experimental Biology, Washington DC. PARTICIPANTS: Calliandra Harris - Technician; Winyoo Cowanadisai, PhD - Post Doctoral Fellow; Michael Satre, PhD, Research Associate Work was funded in part by Mitsubishi Chemical Co., Japan TARGET AUDIENCES: Basic Research directed at those with nutritional, biochemical , and biomedical interests. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
Work was completed that indicated PQQ improves mitochondrial respiratory control or stimulate mitochondrial biogenesis owing to PQQ mediated regulation of PPAR-gamma coactivator-1 alpha (PGC-1 alpha) and nuclear respiratory factors that control mitochondrial gene transcription and mitochondrial DNA replication. PQQ elicited modulation of PGC-1alpha was also associated with a reduction in reactive oxygen species (ROS) in mitochondria and protection against various mitochondrial toxins. Moreover, the phosphorylation of CREB is known to be an important regulator of PGC-1 alpha. The CREB-activated PGC-1alpha transcription pathway is responsive to PQQ leading to increases in mtDNA, cytochrome c and cytochrome oxidase expression and succinate dehydrogenase activity as a functional marker of mitochondriogenesis. The expression of phase I and II biotransformation enzymes was also examined with respect to experimental diet composition and with and without the addition of the bi-functional inducer flavone to determine for optimal expression. Enzymatic activity and mRNA levels of cytochrome P450 monooxygenase (CYP) isoforms (CYP1A1, CYP1A2, CYP2B1/2) and glutathione-S-transferase (GST) isoforms (GSTA, GSTM, and GSTP) were used as indices for the changes in expression. An amino acid based (AA) diet and a semi-purified egg white (EW) diet were designed to include similar levels of nutrients and were compared to a standard laboratory chow (SC) diet. The increase in phase I and II enzyme expression observed in response to flavone was most dynamic when the AA-based diet was used (often >20-fold for given isoform enzymatic activities and >200-fold for specific mRNAs), followed by the EW diet (10 to 20-fold and 100 to 200-fold, respectively). The SC diet resulted in a higher level of background expression of CYP and GST isoforms and as a consequence the observed fold increases in CYP and GST isoforms (enzymatic and mRNA levels) were substantially less (1 to 10-fold and 1 to 150-fold, respectively), when the SC diet fed group with or without flavone was compared to corresponding data from AA- or EW-fed groups.
Publications
- Rucker, RB, Keen CL, Fascetti A, Trace Minerals, In: Clinical Biochemistry of Domestic Animals, Sixth Edition (Ed.: J Jerry Kaneko, John H Harvey, Michael L Bruss) Academic Press, San Diego, CA, 2008, p. 663-694.
- Rudolf JL, Bauerly KA, Tchaparian E, Rucker RB, Mitchell AE. The influence of diet composition on phase I and II biotransformation enzyme induction. Arch Toxicol. 2008 82:893-901.
|
Progress 01/01/07 to 12/31/07
Outputs
OUTPUTS: The work is largely basic science in nature, however, much of its associated research activity included mentoring in an apprentice setting three undergraduates, one who is a minority in the MURALS program. The work also supports activities of a post-doctoral scholar. Work during the review period was reported at Experimental Biology, Washington DC, 2007 and shared with Mitsubishi Gas and Chemicals, who are the World's suppliers of pyrroquinoline quinone (PQQ). Much of what was developed as a product of the work demonstrated that PQQ has applications as a novel cell-signaling molecule, associated with mitochondriogenesis. In this regard, we are at the initial stages of developing several collaborations (e.g. with Mitsubishi Gas and Chemical) that we hope will develop into either longer-term research support and/or possible patent application arrangements.
PARTICIPANTS: Robert Rucker, Principle Investigator Calliandra Harris, Technician Winyoo Chowanadisai, Post-doctoral Fellow Rachel Handley, Lab Assistant, Student Edwin LI, Lab Assistant, Student Anitra Smith, Student Partner Organization - Mitsubishi Gas Chemical Co. Tokyo Japan
TARGET AUDIENCES: The target audience includes mostly those whose efforts are fundamental and basic to nutrition. The work is not at the translational stage at this time.
PROJECT MODIFICATIONS: There will be no major changes, except to focus more on defining the fundamental role of PQQ as a novel dietary biofactor.
Impacts
Basic discoveries associated with the work on PQQ and related projects may have far-reaching and important impact on the ways in which future investigators approach studies on biofactors in food. For example, we are in the process of summarizing methodological approaches that show that dietary complexity influences most biotransformation or xenobiotic and/or cell-signaling pathways. The less refined the diet the greater the influence on these pathways. This is likely due to exposure to exogenous phytochemicals present in the less refined or natural diets. Following exposure to activators of CYP1A1, CYP1A2, and CYP2B1/2 (isoforms of cytochrome P450) and GSTA, GSTM, and GSTP (isoforms of glutathione-S-transferase), relative to background (no activation), these enzymes were stimulated 10 to 200 fold (enzymatic activity and respective mRNA levels). Accordingly, we have used this information to develop methods for amplifying metabolic signals in response given biofactors of
nutritional interest. In particular, the approaches have been useful in our studies related to PQQ. For example, we have shown that PQQ confers resistance to acute oxidative stress, and PQQ does this by acting as a cell-signaling agent. Moreover, PQQ deficiency influences the mitochondrial content of heart and liver and impacts the metabolism of compounds oxidized via mitochondrial and peroxisomal pathways. When rats are fed diets devoid of PQQ, there is impaired reproduction, slower neonatal growth, and a reduction in mitochondria in liver and cardiac muscle. Because of mitochondria's central role in metabolism and cardiovascular protection, and based on our previous observations and those of others regarding PQQ status, we propose that PQQ could be important in optimally adding in fat metabolism and clearance. We have also identified about 300-400 genes that appear sensitive to changes in PQQ nutritional status using a CodelinkTM microarray system designed to analyze over 10,000
transcripts. Changes in PQQ status in rats induce striking changes in PGC-1alpha, nuclear respiratory factor (NRF-1 and NRF-2) mRNA levels along with down-stream signaling molecules or indicators of mitochondrial function. Both cellular and in vivo studies are utilized. We predict that the results from these studies will provide or contribute to new paradigms in understanding the molecular mechanism by which certain diet derived biofactors function. We have also continued our collaboration with Carl Keen's group as it relates to studies important to cell-signaling (CA-D*-NTR-5908-H, 0166119, Hatch, DRUG AND DISEASE INDUCED TRACE ELEMENT DEFICIENCIES).
Publications
- Zempleni J, Rucker RB, Suttie, McCormick D (Editors) 2007 The Handbook of Vitamins, Taylor & Francis, NYC, NY. pp. 1-575
- Rucker RB, Bauerly KA. Pantothenic acid (Chapter 9), In: Zempleni J, Rucker RB, Suttie, McCormick D (Editors) 2007 The Handbook of Vitamins, Taylor & Francis, NYC, NY. pp. 289-314
- Johnson CF, Steinberg FM, Rucker RB, Ascorbic Acid (Chapter 15) In: Zempleni J, Rucker RB, Suttie, McCormick D (Editors) 2007 The Handbook of Vitamins, Taylor & Francis, NYC, NY. pp. 489-50
- Rucker RB. 2007 Allometric scaling, metabolic body size and interspecies comparisons of basal nutritional requirements. J Anim Physiol Anim Nutr (Berl). 2007; 91:148-156.
- Yang SJ, Keen CL, Lanoue L, Rucker RB, Uriu-Adams JY. 2007 Low nitric oxide: a key factor underlying copper-deficiency teratogenicity. Free Radic Biol Med. 43:1639-48.
|
Progress 01/01/06 to 12/31/06
Outputs
In mice and rats, pyrroloquinoline quinone (PQQ) dietary status can influence neonatal growth and development. However, mechanisms underlying such effects have been elusive. However, recent gene array analyses (CodeLink rat Bioarrays, Amersham Bioscience) together with metabolic data from animals fed diets with or without added PQQ (nM amounts) suggest genes important to mitochondrial-related pathways are targets. Clustering algorithms have identified 450 genes including ESTs (out of 10000) that are sensitive to changes in dietary PQQ status. Functional alterations that correspond to the changes in gene expression (PQQ devoid versus PQQ supplemented diets) include: a decrease in mitochondrial content in neonates, perturbations in the apparent rates of lipid and amino acid oxidation; eventual reproductive failure. Because the diet is a source of PQQ, PQQ may be nutritionally important, particularly to the neonate; potentially acting as a peroxisome proliferator
activated receptor agonists or co-activator. Moreover, the effects of copper deficiency on mouse yolk sac vasculature and expression of angiogenic mediators was studied. Copper deficiency results in abnormal development and increased 3-nitrotyrosine in Cu deficient mouse embryos.
Impacts
PQQ may be important as a growth promoting substance in eukaryotes. We have demonstrated that PQQ is present in many tissues. PQQ role in growth and improvements in reproductive performance has direct impact animal production and performance. We can now hypothesize that a mode of action for PQQ is as an agonist for PPAR or related regulatory pathways.
Publications
- Beckers M, Lanoue L, Keen CL, Rucker RB, Uriu-Adams JL., 2006. Abnormal development and increased 3-nitrotyrosine in Cu deficient mouse embryos. Free Radical Biology Medicine 40:35-44.
- Stites TE, Storms DL, Bauerly K, Mah J, Harris C, Fascetti A, Rogers O, Tchaparian E, Satre M, Rucker RB., 2006. Pyrroloquinoline Quinone: Modulation of mitochondrial quantity and function in mice. Journal of Nutrition 136:390-396.
- Rucker, RB Kosonen, T., 2006. "Chemical Physical Properties of Amino Acids" In: Biochemical, Physiological, & Molecular Aspects of Human Nutrition. [Edited by] Martha H. Stipanuk. 2nd ed., Saunders Elsevier, St. Louis.
- Steinberg, FM & Rucker, RB., 2006. Water Soluble Vitamins. In: Handbook of Food Technology, Dekker Press, NY, NY, Chapter 10: 1-18.
- Miller, JW, Rogers LM, Rucker RB., 2006. Pantothenic Acid. In: Present Knowledge in Nutrition (Eds. E. E. Ziegler, Filer, L.J.) ILSI Press, Wash. D.C.
- Bauerly KA, Storms D, Harris CB, Hajizadeh S, Sun MY, Cheung CP, Satre MA, Fascetti AJ, Tchaparian E, and Rucker RB., 2006. Pyrroloquinoline Quinone Nutritional Status Alters Lysine Metabolism and Modulates Mitochondrial DNA Content in the Mouse and Rat. Biochim. Biophys, Acta 1760:1741-1748.
- Yang SJ, Uriu-Adams JY, Keen CL, Rucker RB, Lanoue L., 2006. Effects of copper deficiency on mouse yolk sac vasculature and expression of angiogenic mediators. Birth Defects Res B Dev Reprod Toxicol. 77:445-454.
|
Progress 01/01/05 to 12/31/05
Outputs
In mice and rats, pyrroloquinoline quinone (PQQ) dietary status can influence neonatal growth and development. However, mechanisms underlying such effects have been elusive. Potential roles for PQQ as an antioxidant or vitamin-like cofactor have been suggested. However, recent gene array analyses (CodeLink rat Bioarrays, Amersham Bioscience) together with metabolic data from animals fed diets with or without added PQQ (nM amounts) suggest genes important to mitochondrial-related pathways are targets (e.g. peroxisomal and MAP kinase regulated pathways). Clustering algorithms have identified 450 genes including ESTs (out of 10000) that are sensitive to changes in dietary PQQ status. Functional alterations in metabolism and systemic functions that correspond to the changes in gene expression include: a decrease in mitochondrial content in neonates, perturbations in the apparent rates of lipid and amino acid oxidation (and levels of key associated enzyme activities);
eventual reproductive failure in immune compromised mice (e.g. BALB/c). In contrast, no differences in lysine metabolism have been observed (cf. Nature. 2005 433:E10-1 and related papers). Using enzymatic or HPLC/ionization mass spectrometry methods to quantify PQQ, a consistent and important finding is its presence in tissues and fluids (e.g. nM concentrations in milk, liver and brain). Because the diet is a source of PQQ, we contend that PQQ may be nutritionally important, particularly to the neonate; potentially acting as a peroxisome proliferator activated receptor agonists or co-activator.
Impacts
PQQ may be important as a growth promoting substance in eukaryotes. We have demonstrated that PQQ is present in many tissues. PQQ role in growth and improvements in reproductive performance has direct impact animal production and performance. We can now hypothesize that a mode of action for PQQ is as an agonist for PPAR or related regulatory pathways.
Publications
- Rucker RB, Storms DH, Sheets A, Tchaparian E, Fascetti A. Identification of PQQ as a vitamin remains tenuous, Nature, 433:E10-1; discussion E11-2 2005
- Uriu-Adams JY, Rucker RB, Commisso J, Keen CL. Diabetes and dietary copper alter 67Cu metabolism and oxidant defense in the rat. Nutritional Biochemistry, 16:312-20 2005
- Dahl SLM, Rucker RB, Niklason LE. Effects of Copper and Crosslinking on the Extracellular Matrix of Tissue Engineered Arteries. Cell Transplantation, 14:367-74 2005
|
Progress 01/01/04 to 12/31/04
Outputs
Pyrroloquinoline quinone (PQQ) acts as a growth factor in neonatal and young mice, is present in human milk and tissues, and affects a wide variety of systemic functions when deficient in diets. Recent work has focused on defining mechanisms to explain why PQQ improves indices of growth and development. Gene array/informatics analyses of PQQ's impact on liver gene expression were carried out using PQQ-supplemented and deprived rats as a model. The Code Link rat whole genome bioarray system from Amersham was used for the assessment, because of its complete coverage of the rat genome (targets 34,000 transcripts and ESTs, including over 29,000 well substantiated rat genes), accuracy, sensitivity and specificity. We also examined the recent assertion that PQQ is a vitamin-like cofactor for the mammalian enzyme, 2-aminoadipic 6-semialdehyde (AAS) dehydrogenase (T Kasahara and T Kato, Nature 422: 832, 2003). We observed (summations from four separate experiments) that the
plasma aminoadipic acid to lysine ratio and levels of AAS dehydrogenase activity in liver are not changed by PQQ deprivation. However, as little as one nanomolar PQQ in diets causes changes in genes associated with cell differentiation, growth, vascular permeability, and inflammation (stress). Many of the changes are 10-fold or more (both up and down regulated) and appear to account for most of the phenotypic changes that are noted in PQQ deprived mice and rats. Examples of down regulated liver-related genes in PQQ deprived rats include: insulin-like growth factor, endothelin receptor A, Ca binding protein, glucagon induced protein kinase A, aquaporin 8, opioid receptor, sigma 1, members of the CCR4 transcriptional regulatory complex, CREG, glucokinase, preimplantation protein 3, cadherin, asparaginase, and cathepsin H.
Impacts
PQQ may be important as a growth promoting substance in eukaryotes. We have demonstrated that PQQ is present in many tissues. PQQ promotes growth and improves reproductive performance, which has direct impact particularly on production animal (dairy and meat) performance. For the first time, it should be possible, through the careful analysis of gene arrays, to assess potential mechanisms of action.
Publications
- Rucker, RB and Lanoue, L. 2004 Trace Minerals: Metabolism and Deficiency (Copper, Zinc, Manganese, and Selenium) In: Encyclopedia of Gastroenterology (Eds: Alpers, DH et al.), Academic Press, Imprint of Elsevier Science, San Diego. pp. 502-507.
- Changtai Cui, Uriu-Adams, J, Keen, CL and Rucker, RB. 2004 Vanadate causes cellular accumulation of copper and decreased lysyl oxidase activity. Toxicology Applied Pharmacology 199:35-43.
- Rucker, RB and Steinberg, FM 2004 Vitamin C In: Encyclopedia of Biological Chemistry, 4:367-371, Elsevier Inc. London, San Diego
- Rucker, RB, Storms, DH, Sheets, A, Tchaparian, E 2004 Identification of PQQ as a vitamin remains tenuous, Nature, in press.
- Steinberg, FM and Rucker, RB. 2005 Water Soluble Vitamins. In: Handbook of Food Technology, Dekker Press, NY, NY, in press
|
Progress 01/01/03 to 12/31/03
Outputs
We have reported previously that pyrroloquinoline quinone (PQQ) is a growth factor in neonatal and young mice, is present in milk, and affects a wide variety of systemic functions when deficient in diets. Recent work has focused on defining mechanisms and interactions with antagonists and mitochondrial complex I inhibitors. When PQQ is added to a chemically defined, but otherwise nutritionally complete diet, there is improvement in indices of mitochondrial function. In 35-day-old PQQ-deprived mice, the mitochondrial content per cell was reduced compared to age- and weight-matched PQQ-supplemented mice. Although PQQ deprivation did not abnormally alter the P:O ratio of mice, the respiratory control ratio (RCR) values were positively correlated with body weight (r2=0.45). Mice were also gavaged with 0 to 4 ug PQQ/g body weight daily for 14 days. At each PQQ level, DPI (diphenylene iodonium) was administered at 0 to 1.6 ug DPI/g body weight. Mice that received 3 0.4 ug
DPI/g body weight and no PQQ, lost weight and had lower whole blood glucose levels than PQQ-supplemented mice. In addition, we have examined selected details presented in a recent paper by T Kasahara and T Kato (Nature 422: 832, 2003), who have claimed the discovery of the first PQQ-dependent enzyme in animals, i.e. PQQ-dependent 2-aminoadipic 6-semialdehyde (AAS)-dehydrogenase (AASDH; EC 1.2.1.31), which is said to catalyzes the oxidation of AAS. Although we have yet to be able to confirm their findings, we were able to demonstrate amino acid metabolomic patterns that are consistent with compromised mitochondrial and oxidative functions. Regarding other work, we demonstrated that sodium metavanadate, a broad-spectrum inhibitor of ATPase activity, can induce alterations in extracellular matrix (ECM) production and metabolism that are similar to those observed in dietary copper deficiency or -aminoproprionitrile exposure. In skin and tendon, and cultured fibroblasts, cellular copper
increased progressively in response to metavanadate exposure. The activity of the plasma cuproenzyme, ceruloplasmin, principally secreted from liver, was not changed in response to dietary metavanadate, whereas the functional activity of a cuproprotein, lysyl oxidase, secreted principally from cells important to ECM production was inhibited in response to metavanadate exposure. These data indicate that of the many ATPases inhibited by metavanadate, the P-ATPase-7A that is involved in copper egress and lysyl oxidase activation may be particularly sensitive.
Impacts
PQQ may be important as a cofactor in eukaryotes. We have shown previously that PQQ is present in tissues. Establishing the function or identifying the mechanism by which cofactors act often has health and disease implications. PQQ promotes growth and improves reproductive performance, which has direct impact particularly on production animal (dairy and meat) performance. The work on vanadium adds a new dimension to its potential as a toxicant.
Publications
- Steinberg, FM & Rucker, RB. 2003 Water Soluble Vitamins. In: Handbook of Food Technology, Dekker Press, NY, NY, in press
- In: Handbook of Food Enzymology, Vol. II-Section A (Eds: J. Whitaker et al.), Dekker Press, NYC, NY. 2003 * Rucker R.B., Mitchell A. E., Tchaparian E., and Last J. Lysyl Oxidase, pp. 493-502. * Robert Rucker, Ana Samimi and Jerald Last. Prolyl 4-Hydroxylase, pp. 477-484. * Ana Samimi, Jerold A. Last, Lucas C. Armstrong and Robert B. Rucker. Lysyl Hydroxylase, pp. 484-492.
- Susan N. Hawk, Louise Lanoue, Carl L. Keen, Catherine L. Kwik-Uribe, Robert B. Rucker, Janet Y. Uriu-Adams 2003 Copper-Deficient Rat Embryos Are Characterized by Low Superoxide Dismutase Activity and Elevated Superoxide Anions. Biol Reprod 68: 896-903.
- Steinberg F, Stites TE, Anderson P, Storms D, Chan I, Eghbali S, Rucker R. 2003 Pyrroloquinoline quinone improves growth and reproductive performance in mice fed chemically defined diets. Exp. Biol. Med. 228:160-166.
- Keen CL, Jue T, Tran CD, Vogel J, Downing RG, Iyengar V, Rucker RB. 2003 Analytical methods: improvements, advancements and new horizons. J Nutrition 133:1574S-1578S
- Keen CL, Hanna LA, Lanoue L, Uriu-Adams JY, Rucker RB, Clegg MS. 2003 Developmental consequences of trace mineral deficiencies in rodents: acute and long-term effects. J Nutrition 133:1477S-1480S.
- Rucker RB & Lanoue L. 2003 Essential Trace Elements: Copper, Zinc, Manganese, and Selenium Regulation and Functions In: (Encyclopedia of Gastroenterology, Eds. Alpers, DH et al.), Academic Press, Imprint of Elsevier Science, San Diego, in press
|
Progress 01/01/02 to 12/31/02
Outputs
Pyrroloquinoline quinone is present in milk and affects a wide variety of systemic functions when deficient in diets. Recent work has focused on defining mechanisms and interactions with antagonists, mitochondrial complex I inhibitors, riboflavin, and selected antioxidants. In this regard: 1) PQQ analogs that are incapable of redox cycling (e.g. ethylene and cis 1,2 diaminocyclohexane) do not cause adverse effects in vivo or in vitro (e.g. as inhibitors of bacterial glucose dehydrogenase, GDH) at 100X-1000X the PQQ concentrations used in assays or diets. Imidazoloquinoline quinone, the most predominant PQQ adduct, however, can be reversibly converted to PQQ in vivo, but does not function as a GDH substrate. 2) PQQ also reverses the effects of rotenone and diphenylene iodonium (DPI) at equimolar (or less) concentrations in assays in vitro for mitochondrial function, and in vivo (e.g. normalizes reduced growth and glucose levels caused by DPI). 3) PQQ does not appear to
interact with riboflavin in nutritional models, although can serve as a cofactor/substrate for some riboflavin-requiring reductases. 4) In chemical assays, PQQ is not an efficient peroxyanion scavenger, but interacts readily with superoxide in assays that measure redox cycling more efficiently (100X-1000X on a molar basis) than common phyto- and polyquinone compounds
Impacts
PQQ may be important as a potential cofactor in eukaryotes. We have shown previously that PQQ is present in tissues as free PQQ and as amino acid adducts. Establishing the function or identifying the mechanism by which cofactors act often has health and disease implications. PQQ promotes growth and improves reproductive performance, which has direct impact on production animal (dairy and meat) performance.
Publications
- 1.Robert B. and Francene M. Steinberg 2002 Vitamin Requirements: Relationship to Basal Metabolic Need and Functions. Biochemistry and Molecular Biology Education 2002 30: 86-89.
- 2.Rucker R, Storms D. 2002 Interspecies comparisons of micronutrient requirements: metabolic vs. absolute body size. J Nutr. 132:2999-3000.
|
Progress 01/01/01 to 12/31/01
Outputs
Most of our effort in this review period has gone into defining the physiological roles for compounds, such as pyrroloquinoline quinone (PQQ). With regard to growth, reproductive outcome, Balb/c mice were used as physiologic models and fed a chemically defined, amino acid-based diet with or without varying amounts PQQ. The diets were fed to virgin Balb/c mice for 8 weeks prior to breeding. At weaning, the pups from successful pregnancies were fed the same diet as their respective dams. Mice fed diets devoid of PQQ or at low PQQ concentrations (less than 150ng/g diet) grew at slower rates than mice fed diets supplemented with PQQ (greater than 300ng/g diet) Reproductive performance was also compromised in PQQ-deficient mice. For example, conception (percentage of females giving live births) and fertility (percentage of births) were decreased in mice deprived of dietary PQQ. Although successful mating (confirmed vaginal plugs) was not affected by PQQ supplementation,
pup viability (number of pups at parturition/number of pups at day 4 of lactation) was decreased in PQQ-deprived mice. PQQ deprivation, or its impact on early growth, also modulated the expression of lysyl oxidase and type I procollagen alpha-1-chains (I-procollagen-alpha-1) steady-state mRNA levels. In neonatal mice, the steady-state mRNA levels of lysyl oxidase and I-procollagen-alpha-1 mRNA were positively correlated with body weight. Values for lysyl oxidase protein accumulation in PQQ-deficient mice also tended to be lower than corresponding values from PQQ-supplemented or -repleted mice. Skin collagen solubility was increased in PQQ-deprived mice. These results indicate that PQQ supplementation can improve reproductive performance and growth, and may modulate neonatal extracellular matrix expression and maturation in mice when fed chemically defined, but otherwise nutritionally complete diets. Continuing effort will focus on improvements in analytical and assessment procedures
and protocols.
Impacts
PQQ may be important as a potential cofactor in eukaryotes (this category includes mammals and "higher" animals). We have shown previously that PQQ is present in tissues as free PQQ and as amino acid adducts. Establishing the function or identifying the mechanism by which cofactors act often has health and disease implications. PQQ promotes growth and improves reproductive performance, which has direct impact on production animal (dairy and meat) performance.
Publications
- Tracy E. Stites, Tracey R. Sih, and Robert B. Rucker. 2000. Synthesis of 14C-pyrroloquinoline quinone (PQQ) in E. coli using genes for PQQ synthesis from K. pneumonia. Biochimica Biophysica Acta 1524: 247-252.
- Rucker, R. B. (Principle Editor). 2001. The Handbook of Vitamins (Eds. R.B. Rucker, J. Suttie, D. McCormick and L. Macland) Dekker Publishing, NYC, NY, pp. 1-600. A) Robert Rucker, Preface for the Handbook of Vitamins, pp. v-vii Johnson, C., F. L. Steinberg, and Rucker, R. B, Ascorbic Acid, Chapter 15, pp. 555 - 568.
- Miller, J.W., L.M. Rogers, and R.B. Rucker. 2001. Pantothenic Acid. In: Present Knowledge in Nutrition (Eds. E. E. Ziegler and L.J. Filer) ILSI Press, Wash. D.C., Chapter 24, pp.253-260.
- Robert Rucker, Tracy Stites, Yasushi Suzuki, Francene Steinberg, and David Storms. 2001. Physiological Importance of pyrroloquinoline quinone. Vitamin (Japanese) 75: 381-387.
- Similar to: Robert Rucker, Tracy Stites, Francene Steinberg, and Alyson Mitchell. 2000. Physiological Importance of pyrroloquinoline quinone. In: Biochemical and molecular Biology of Vitamin B-6 and PQQ-dependent Proteins (Eds. A. Iriarte, H. Kagan, M. Martinez-Carrion), pp. 61-66. Birkhauser Verlag, Basal.
- Robert B. Rucker, Changtai Cui, Eskouhie H. Tchaparian, Alyson E. Mitchell, Michael Clegg, Janet Y. Uriu-Hare, Brian Rucker, Tracy Stites, and Carl L. Keen. 2000. Dietary Copper, Vanadate, Lysyl Oxidase Activity and Lysine Tyrosyl Quinone Formation, Proceedings of the10th International Symposium on Trace Elements in Man and Animals, (Editor, Alain Favier), Volume 10:929-932.
|
|